Somatomedin C ("SMC") is an insulin-like growth factor that appears to be the critical protein signalling tissue growth following secretion of growth hormone from the pituitary.
The amino acid sequence of human SMC was reported by E. Rinderknecht and R. E. Humble, J. Biol. Chem., 253, pp. 2769-76 (1978). It consists of a single chain polypeptide of 70 amino acids, cross-linked by three disulfide bridges. The calculated molecular weight is 7649. SMC displays extensive homology to proinsulin. For example, SMC amino acids 1 to 29 are homologous to the insulin B chain and SMC amino acids 42-62 are homologous to the insulin A chain. The connecting chain in SMC, however, shows no homology to the C peptide of proinsulin and SMC also has a C-terminal octapeptide not found in proinsulin.
SMC displays numerous growth promoting effects in vitro, such as stimulation of DNA, RNA, protein and proteoglycan synthesis [E. Rinderknecht and R. E. Humble, Proc. Natl. Acad. Sci USA, 73, pp. 2365-69 (1976); B. Morell and E. R. Froesch, Eur. J. Clin. Invest., 3, pp. 119-123 (1973); E. R. Froesch et al., Adv. Mental. Disord., 8, pp. 211-35 (1975); A. E. Zingg and E. R. Froesch, Diabetologia, 9, pp. 472-76 (1973); E. R. Froesch et al., Proc. Natl. Acad. Sci. USA, 73, pp. 2904-08 (1976). It also stimulates ornithine decarboxylase and cell proliferation [B. Morrel and E. R. Froesch, supra; G. K. Haselbacher and R. E. Humble, J. Cell. Physiol., 88, pp. 239-46 (1976)]. In vivo, SMC stimulates growth in rats made growth-hormone deficient by hypophysectomization [E. Schoenle et al., Nature, 296, pp. 252-53 (1982)].
Like growth hormones, SMCs are somewhat species specific. However, SMC from one species may be biologically active in another species lower in the evolutionary scale. For example, human SMC is believed to be useful in promoting growth in cattle, swine and chickens. In laboratory animals, SMC has shown growth stimulating effects similar to those of natural human growth hormone. However, SMC is thought to be advantaged over human growth hormone because SMC is a central mediator of the growth response. Accordingly, it is a more direct regulator of growth than growth hormone.
In addition to SMC's use in treating certain forms of growth disturbances, such as dwarfism and muscle atrophy, it is also useful for stimulating tissue growth in specific areas, such as in connection with the healing of wounds, injuries and broken bones.
SMC, however, has not fulfilled its clinical potential as a tissue growth stimulator because it is available in only minute amounts through purification from human blood. Accordingly, other methods are required to overcome this lack of commercial and clinically useful quantities of SMC.
One such approach might involve the use of recombinant DNA technology to produce SMC in hosts transformed with a DNA sequence coding for it. However, this approach has not proved useful in preparing large amounts of SMC, because the expression yields of SMC in various E.coli hosts have been too low to provide economically useful or commercial quantities of SMC.